Improving early cholecystectomy rate in acute cholecystitis with an evidence-based local multidisciplinary protocol and a surgical audit: single-center experience through an Acute Care Surgery Division.

PURPOSE: To analyze if, after implementation of an evidence-based local multidisciplinary protocol for acute cholecystitis (AC), an intermediate surgical audit could improve early cholecystectomy (EC) rate and other therapeutic indicators. METHODS: Longitudinal cohort study at a tertiary center. The local protocol, promoted, created, and periodically revised by the Acute Care Surgery Unit (ACSu) was updated and approved on March 2019. A specific registry was prospectively fulfilled with demographics, comorbidity, type of presentation, diagnostic items, therapeutic decision, and clinical course, considering both non-operative management (NOM) or cholecystectomy, early and delayed (EC and DC). Phase 1: April 2019-April 2021. A critical analysis and a surgical audit with the participation of all the involved Departments were then performed, especially focusing on improving global EC rate, considered primary outcome. Phase 2: May 2021-May 2023. Software SPSS 23.0 was used to compare data between phases. RESULTS: Initial EC rate was significantly higher on Phase 2 (39.3%vs52.5%, p < 0.004), as a significantly inferior rate of patients were initially bailed out from EC to NOM because of comorbidity (14.4%vs8%, p < 0.02) and grade II with severe inflammatory signs (7%vs3%, p < 0.04). A higher percentage of patients was recovered for EC after an initial decision of NOM on Phase 2, but without reaching statistical significance (21.8%vs29.2%, n.s.). Global EC rate significantly increased between phases (52.5%vs66.3%, p < 0.002) without increasing morbidity and mortality. A significant minor percentage of elective cholecystectomies after AC episodes had to be performed on Phase 2 (14%vs6.7%, p < 0.009). Complex EC and those indicated after readmission or NOM failure were usually performed by the ACSu staff. CONCLUSION: To adequately follow up the implementation of a local protocol for AC healthcare, registering and periodically analyzing data allow to perform intermediate surgical audits, useful to improve therapeutic indicators, especially EC rate. AC constitutes an ideal model to work with an ACSu.

Perioperative and oncologic outcomes of interval colectomy performed by acute care surgeons after stenting as a bridge to surgery for left-sided malignant colonic obstruction are non-inferior to the outcomes of colorectal surgeons in the elective setting: single center experience.

PURPOSE: To analyze if perioperative and oncologic outcomes with stenting as a bridge to surgery (SEMS-BS) and interval colectomy performed by acute care surgeons for left-sided occlusive colonic neoplasms (LSCON) are non-inferior to those obtained by colorectal surgeons for non-occlusive tumors of the same location in the full-elective context. METHODS: From January 2011 to January 2021, patients with LSCON at University Regional Hospital in Málaga (Spain) were directed to a SEMS-BS strategy with an interval colectomy performed by acute care surgeons and included in the study group (SEMS-BS). The control group was formed with patients from the Colorectal Division elective surgical activity dataset, matching by ASA, stage, location and year of surgery on a ratio 1:2. Stages IV or palliative stenting were excluded. Software SPSS 23.0 was used to analyze perioperative and oncologic (defined by overall -OS- and disease free -DFS-survival) outcomes. RESULTS: SEMS-BS and control group included 56 and 98 patients, respectively. In SEMS-BS group, rates of technical/clinical failure and perforation were 5.35% (3/56), 3.57% (2/56) and 3.57% (2/56). Surgery was performed with a median interval time of 11 days (9-16). No differences between groups were observed in perioperative outcomes (laparoscopic approach, primary anastomosis rate, morbidity or mortality). As well, no statistically significant differences were observed in OS and DFS between groups, both compared globally (OS:p < 0.94; DFS:p < 0.67, respectively) or by stages I-II (OS:p < 0.78; DFS:p < 0.17) and III (OS:p < 0.86; DFS:p < 0.70). CONCLUSION: Perioperative and oncologic outcomes of a strategy with SEMS-BS for LSCON are non-inferior to those obtained in the elective setting for non-occlusive neoplasms in the same location. Technical and oncologic safety of interval colectomy performed on a semi-scheduled situation by acute care surgeons is absolutely warranted.

Diagnosis and Treatment of Carpal Tunnel Syndrome in A Tertiary Care Center in Mexico City.

BACKGROUND: Carpal tunnel syndrome is the most common peripheral neuropathy affecting patients at productive age and has an important economical impact on those who suffer it. This study assessed the diagnostic performance of carpal tunnel syndrome´s signs and described the epidemiology at a tertiary care center in Mexico City. METHODS: All patients diagnosed with carpal tunnel syndrome during a five-year period were included. Demographic data, electromyography results, positive clinical signs and the severity score according to the Italian scale were recorded. Diagnostic accuracy of Tinel and Phalen´s signs were calculated via odds ratio. RESULTS: Totally, 650 patients were diagnosed and treated during a five-year period, 84% were female and 16% male, and the mean age was 55.8 years. The associated comorbidities were trigger finger (36.1%), thyroid disease (25.6%) and diabetes (20%). Diagnosis yielded for Phalen and Tinel signs were variable in each of the study groups (males and females) and showed to be beneficial in diagnosis of the disease. CONCLUSION: Carpal tunnel syndrome is a complex disease in which clinical signs remain the cornerstone of diagnosis. Extension studies are useful to assess the severity of the disease.

Descriptive observational study on early functional recovery and postoperative pain in knee joint replacement surgery. / Estudio observacional descriptivo sobre recuperación funcional temprana y dolor postoperatorio en cirugía de reemplazo articular de rodilla.

INTRODUCTION: The management of postoperative pain in joint replacement surgery represents a challenge. Therefore, the advent of new strategies in the management of pain such as local infiltration analgesia (LIA) and the adductor canal block, allowed an adequate postoperative pain control and early rehabilitation of the patient in total knee arthroplasty. MATERIALS AND METHODS: A descriptive, observational and longitudinal study of a prospective cohort of patients operated by the group of joint replacements between September 29, 2017 and November 30, 2017 was conducted. They were evaluated with the analog pain scale for postoperative pain at 5 different times (1:Upon leaving recovery; 2:On the first postoperative day; 3:Before initiating in-hospital physical therapy; 4:At the end of physical therapy, and 5:Upon departure from the clinic). RESULTS: Of the 141 patients operated on, 70.9% of the patients were managed with LIA and 29.1% with adductor canal block. There were no differences between groups in postoperative pain assessment during the 5 different times (P≥.45). DISCUSSION: Our results indicate that LIA and the adductor canal blockade demonstrated the same efficacy for the control of postoperative pain and rehabilitation.

Water-in-oil organogel based emulsions as a tool for increasing bioaccessibility and cell permeability of poorly water-soluble nutraceuticals.

The use of organogels in food and pharmaceutical sciences has several technical problems related with restricted diffusion of the drugs and lack of a proper gelator molecule. These features are important into the new product design. An alternative to improve technological properties in organogels is the use of emulsions. However, there is a lack of knowledge about the behavior on bioaccessibility and permeability of bioactives loaded into organogel-based emulsions. The objective of the present experimental work was to study the physical properties of organogel-based emulsions made with vegetable oil loaded with three different bioactives (betulin, curcumin and quercetin) and the influence on their bioaccessibility. Organogels were made of canola or coconut oils and myverol as gelator (10% w/w). Water-in-oil emulsions (at 5, 10 and 12.5 wt% of water content) were prepared by mixing the melted proper organogel and water (80 °C) under high shear conditions (20,000 rpm). Micrographs, rheological tests (amplitude, frequency, temperature sweeps and creep-compliance measurements), DSC and particle size analysis were performed to samples. In vitro digestion (oral, gastric and intestinal phase), lipolysis assays, bioaccessibility and permeability tests by cell culture of Caco-2 were made. Organogels of coconut oil have shown poor emulsification properties.

Analysis of Intrahospital Mortality in Patients With Lung Transplant Due to Diffuse Parenchymal Lung Disease.

BACKGROUND: Patients with diffuse parenchymal lung disease (DPLD) have the poorest survival rates both before and after lung transplantation (LT). Early mortality among LT patients as a result of DLPD is estimated at 10% to 20%. The aim of the study was to assess intrahospital mortality after LT procedures for DLPD and to identify factors in the recipient, donor, intra- and postoperative periods that might improve early outcomes. METHODS: A retrospective, observational, cohort, single-hospital study was conducted. Data from 67 patients with LT patients owing to DPLD were recorded between October 2008 to June 2017 in Madrid, Spain. RESULTS: Out of 67 LT recipients with DPLD, 51 had idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), 6 nonspecific interstitial pneumonia (NSIP), and 10 other DPLD. Intrahospital mortality took place in 13.4% of patients, with a median survival time of 34 days (interquartile range [IQR], 27.50-66). In the preoperative period, there were no differences in the recipients' demographic and hemodynamic characteristics, respiratory function, or time spent in the waiting list, except higher doses of systemic steroids in nonsurvivors (prednisone 15 vs 10 mg, P = .046). No differences were reported in the donors' characteristics (age, mechanical ventilation hours, PaO2/FiO2). In the intraoperative and postoperative periods, we found differences statistically significant in longer cold ischemia time and development of primary graft dysfunction (PGD) grade 3 in the nonsurvivor group. CONCLUSIONS: The mortality rate in our series was 13.4%, and the main risk factors for intrahospital mortality were longer cold ischemia time and greater incidence of PGD grade 3.

SWI/SNF chromatin remodeling enzymes in melanocyte differentiation and melanoma.

Epidermal melanocytes are pigment-producing cells derived from the neural crest that protects skin from the damaging effects of solar radiation. Malignant melanoma, a highly aggressive cancer, arises from melanocytes. SWI/SNF enzymes are multiprotein complexes that remodel chromatin structure and have extensive roles in cellular differentiation. Components of the complex have been found to be mutated or lost in several human cancers. This review focuses on studies that implicate SWI/SNF enzymes in melanocyte differentiation and in melanoma.

Impact of liver steatosis on the correlation between liver stiffness and fibrosis measured by transient elastography in patients coinfected with human immunodeficiency virus and hepatitis C virus.

We assessed the effect of different hepatic conditions such as fibrosis, steatosis and necroinflammatory activity on liver stiffness as measured by transient elastography in HIV/HCV-coinfected patients. We studied all consecutive HIV/HCV-coinfected patients who underwent liver biopsy and elastography between January 2007 and December 2008. Liver fibrosis was staged following METAVIR Cooperative Study Group criteria. Steatosis was categorized according to the percentage of affected hepatocytes as low (≤10%), moderate (<25%) and severe (≥25%). A total of 110 patients were included. Fibrosis was distributed by stage as follows: F0, n = 13; F1, n = 47; F2, n = 29; F3, n = 18; and F4, n = 3. Liver biopsy revealed the presence of hepatic steatosis in 68 patients (low to moderate, n = 53; and severe n = 15). By univariate regression analysis, fibrosis, necroinflammatory activity, and the degree of steatosis were correlated with liver stiffness. However, in a multiple regression analysis, steatosis and fibrosis were the only independent variables significantly associated with liver stiffness. With a cut-off of 9.5 kPa to distinguish patients with F ≤ 2 from F ≥ 3, elastography led to a significantly higher number of misclassification errors (25%vs 5%; P = 0.014), most of which were false positives for F ≥ 3. Our study suggests that the correlation between liver stiffness and fibrosis as estimated by transient elastography may be affected by the presence of hepatic steatosis in HIV/HCV-coinfected patients.

Heterogeneous SWI/SNF chromatin remodeling complexes promote expression of microphthalmia-associated transcription factor target genes in melanoma.

The microphthalmia-associated transcription factor (MITF) promotes melanocyte differentiation and cell-cycle arrest. Paradoxically, MITF also promotes melanoma survival and proliferation, acting like a lineage survival oncogene. Thus, it is critically important to understand the mechanisms that regulate MITF activity in melanoma cells. SWI/SNF chromatin remodeling enzymes are multiprotein complexes composed of one of two related ATPases, BRG1 or BRM, and 9-12-associated factors (BAFs). We previously determined that BRG1 interacts with MITF to promote melanocyte differentiation. However, it was unclear whether SWI/SNF enzymes regulate the expression of different classes of MITF target genes in melanoma. In this study, we characterized SWI/SNF subunit expression in melanoma cells and observed downregulation of BRG1 or BRM, but not concomitant loss of both ATPases. Re-introduction of BRG1 in BRG1-deficient SK-MEL5 cells enhanced expression of differentiation-specific MITF target genes and resistance to cisplatin. Downregulation of the single ATPase, BRM, in SK-MEL5 cells inhibited expression of both differentiation-specific and pro-proliferative MITF target genes and inhibited tumorigenicity in vitro. Our data suggest that heterogeneous SWI/SNF complexes composed of either the BRG1 or BRM subunit promote expression of distinct and overlapping MITF target genes and that at least one ATPase is required for melanoma tumorigenicity.

Smoking, sun exposure, number of nevi and previous neoplasias are risk factors for melanoma in older patients (60 years and over).

BACKGROUND: Malignant melanoma risk factors have been studied in different geographical area populations. However, no study has focused on risk factors which are more frequently associated to the over 60's age group. METHODS: A case-control study was performed that included 160 patients age > or = 60 years diagnosed of cutaneous melanoma and 318 controls matched for age and sex. Both groups were assessed, by personal interview and physical examination, for different phenotype characteristics (hair and eye color, phototype), the presence of other cutaneous lesions (solar lentigines, actinic keratoses and nevi), degree and type of solar exposure and personal and family past history of cutaneous or non-cutaneous cancer. Differences were evaluated by contingency tables and univariate and multivariate logistic regression. RESULTS: Of 17 factors, those risk factors with a strong effect on the development of melanoma in the elderly were: fair eyes, severe sunburns, years of occupational sun exposure, smoking, > 50 melanocytic nevi and personal history of NMSC and other non-cutaneous neoplasias. CONCLUSIONS: Tobacco smoking is an independent risk factor for cutaneous melanoma in the elderly. Intense (both acute and chronic) sun exposure and constitutional features, such as tumor susceptibility (NMSC, non-cutaneous neoplasias, and multiple nevi) are also associated with melanoma risk. All these factors should help to better design educational campaigns in older people.

[Mitochondrial acetoacetyl-CoA thiolase deficiency: neonatal onset]. / Déficit de acetoacetil-CoA tiolasa mitocondrial: inicio en el período neonatal.

We present the case of a 4-day-old newborn with serious dehydration, polypnea, hypertonus and lethargy. Blood analysis showed severe metabolic acidosis with ketonemia, ketonuria and elevation of the GAP anion. Urine analysis revealed increased excretion of 2-methyl-3-hydroxybutyrate acid, tiglycine, and 2-methylacetoacetate acid. Neonatal onset of mitochondrial acetoacetyl-CoA thiolase (T2) deficiency is exceptional. Most patients have no clinical symptoms in the neonatal period. This entity should be considered in patients with acute metabolic acidosis and ketosis with normal glycemia and aciduria. The urine contains large amounts of 2-methylacetoacetate and its decarboxylation products. In the neonatal period, this inherited disorder of metabolism can produce severe hydroelectrolyte disorders in the form of a gradual process or acute episodes, which can occasionally be fatal.

MyoD can induce cell cycle arrest but not muscle differentiation in the presence of dominant negative SWI/SNF chromatin remodeling enzymes.

Cell cycle arrest is critical for muscle differentiation, and the two processes are closely coordinated but temporally separable. SWI/SNF complexes are ATP-dependent chromatin-remodeling enzymes that have been shown to be required for muscle differentiation in cell culture and have also been reported to be required for Rb-mediated cell cycle arrest. We therefore looked more closely at how SWI/SNF enzymes affect the events that occur during MyoD-induced myogenesis, namely, cell cycle regulation and muscle-specific gene expression, in cells that inducibly express dominant negative versions of Brahma (BRM) and Brahma-related gene 1 (BRG1), the ATPase subunits of two distinct SWI/SNF complexes. Although dominant negative BRM and BRG1 inhibited expression of every muscle-specific regulator and structural gene assayed, there was no effect on MyoD-induced activation of cell cycle regulatory proteins, and thus, cells arrested normally. In particular, in the presence or absence of dominant negative BRM or BRG1, MyoD was able to activate expression of p21, cyclin D3, and Rb, all of which are critical for cell cycle withdrawal in the G1/G0 phase of the cell cycle. These findings suggest that at least one basis for the distinct mechanisms that regulate cessation of cell proliferation and muscle-specific gene expression during muscle differentiation is that SWI/SNF-mediated chromatin-remodeling enzymes are required only for the latter.

Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation.

Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling enzymes that have been implicated in the regulation of gene expression, cell-cycle control and oncogenesis. MyoD is a muscle-specific regulator able to induce myogenesis in numerous cell types. To ascertain the requirement for chromatin remodeling enzymes in cellular differentiation processes, we examined MyoD-mediated induction of muscle differentiation in fibroblasts expressing dominant-negative versions of the human brahma-related gene-1 (BRG1) or human brahma (BRM), the ATPase subunits of two distinct SWI/SNF enzymes. We find that induction of the myogenic phenotype is completely abrogated in the presence of the mutant enzymes. We further demonstrate that failure to induce muscle-specific gene expression correlates with inhibition of chromatin remodeling in the promoter region of an endogenous muscle-specific gene. Our results demonstrate that SWI/SNF enzymes promote MyoD-mediated muscle differentiation and indicate that these enzymes function by altering chromatin structure in promoter regions of endogenous, differentiation-specific loci.

Non-coordinate regulation of 5S rRNA genes and the gene encoding the 5S rRNA-binding ribosomal protein homolog in Neurospora crassa.

In eukaryotes, the levels of ribosomal proteins are coordinately regulated under varying nutritional conditions and at different developmental stages. Little is known about how ribosomal protein levels are coupled to the levels of rRNA. The formation of a ribonucleoprotein particle composed of 5S rRNA and a ribosomal protein is an early step in ribosome assembly. To investigate how these two ribosomal components are regulated in Neurospora crassa, we cloned the gene encoding the 5S rRNA-binding ribosomal protein (crp-4) and developed a novel system for measuring relative 5S rRNA transcriptional rates in vivo, using a reporter RNA derived from the 40S precursor RNA. The reporter RNA is cleaved from the 5S rRNA in vivo and therefore allows us to distinguish between changes in the 5S rRNA transcription rate and 5S rRNA stability. Using this system, we found that transcription of 5S rRNA is constitutive and is not coordinated with the levels of crp-4 mRNA or with 40S rRNA levels during a carbon upshift or a carbon downshift.

Mammalian SWI-SNF complexes contribute to activation of the hsp70 gene.

ATP-dependent chromatin-remodeling complexes are conserved among all eukaryotes and function by altering nucleosome structure to allow cellular regulatory factors access to the DNA. Mammalian SWI-SNF complexes contain either of two highly conserved ATPase subunits: BRG1 or BRM. To identify cellular genes that require mammalian SWI-SNF complexes for the activation of gene expression, we have generated cell lines that inducibly express mutant forms of the BRG1 or BRM ATPases that are unable to bind and hydrolyze ATP. The mutant subunits physically associate with at least two endogenous members of mammalian SWI-SNF complexes, suggesting that nonfunctional, dominant negative complexes may be formed. We determined that expression of the mutant BRG1 or BRM proteins impaired the ability of cells to activate the endogenous stress response gene hsp70 in response to arsenite, a metabolic inhibitor, or cadmium, a heavy metal. Activation of hsp70 by heat stress, however, was unaffected. Activation of the heme oxygenase 1 promoter by arsenite or cadmium and activation of the cadmium-inducible metallothionein promoter also were unaffected by the expression of mutant SWI-SNF components. Analysis of a subset of constitutively expressed genes revealed no or minimal effects on transcript levels. We propose that the requirement for mammalian SWI-SNF complexes in gene activation events will be specific to individual genes and signaling pathways.

Carbon regulation of ribosomal genes in Neurospora crassa occurs by a mechanism which does not require Cre-1, the homologue of the Aspergillus carbon catabolite repressor, CreA.

Transcription of the ribosomal protein and 40S rRNA genes is coordinately regulated during steady state growth and carbon shifts in Neurospora crassa. Recognition sequences for the Aspergillus nidulans carbon catabolite repressor, CreA, overlap transcriptional elements of a 40S rRNA gene and the crp-2 ribosomal protein gene. They also occur in similar locations in the promoters of several other ribosomal protein genes. Substitutions encompassing the -74 and -167 CreA consensus sequences in the crp-2 promoter result in a decrease in transcription. A cDNA encoding the N. crassa homologue of CreA was cloned and designated Cre-1. The Cre-1 protein is 45% identical to CreA from A. nidulans. Cre-1 protein produced in Escherichia coli binds to the CreA sites in the promoters of the 40S rRNA and crp-2 genes. An amino acid change from histidine (92) to threonine changed the Cre-1 binding specificity from (5'G/CC/TGGG/AG3') to (5'G/CC/TGGCG3'). Base substitutions in the Cre-1 binding sites of the crp-2 promoter disrupted binding of wildtype Cre-1 in vitro but had no effect on transcription during steady state growth or carbon shifts, indicating that regulation of ribosomal genes by carbon source is not mediated by Cre-1, but via different proteins binding the Cre-1 sites and the Dde boxes.

[Neuropsychological findings in a case of simulation]. / Hallazgos neuropsicológicos en un caso de simulación.

The case of a malingerer is reported with special emphasis on the neuropsychological findings. The diagnosis of malingering is a challenge to medicine, and neuropsychology can come to be an efficient instrument, once greater experience is achieved, and the results can be systematized and generalized. Nevertheless, it must be kept in mind that the manifestations are specially subject to sociocultural, geographic and temporal factors.

Neuroleptic-induced catatonia: neuroleptic malignant syndrome?

1. The authors describe a case report of catatonia syndrome after administration of depot neuroleptics. 2. Differential diagnosis was made between neuroleptic malignant syndrome or catatonic syndrome complicated by infection. The signs and symptoms observed throughout the patient's course are detailed. 3. A critical review is made of bibliography on the topic, with emphasis on the lack of clear clinical description and poor conceptual definition.